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Biomedical subjects

J D Fox

Publications and source records attributed to J D Fox.

8 recordsLinked to original sources

Detection of herpesvirus DNA in the large intestine of patients with ulcerative colitis and Crohn's disease using the nested polymerase chain reaction.

The prevalence of herpesvirus DNA was examined in inflammatory bowel disease tissue. DNA was extracted from resection and biopsy specimens of the large intestine from patients with ulcerative colitis (n = 21), patients with Crohn's disease (n = 29), and patients with noninflammatory bowel disease (controls) (n = 21). The nested polymerase chain reaction was used to detect viral DNA using primer pairs specific for either cytomegalovirus (CMV), herpes simplex virus 1 (HSV1), human herpesvirus 6 (HHV6), varicella zoster virus (VZV), or Epstein Barr virus (EBV). HSV1 and VZV DNA were not detected in any of tissue samples. There was a high prevalence of CMV (81%), HHV6 (76%), and EBV (76%) DNA in ulcerative colitis tissue compared to Crohn's disease tissues (CMV 66%, HHV6 45%, EBV 55%). Control tissue had a relatively low frequency of CMV (29%) and EBV (19%) DNA but a prevalence of HHV6 DNA similar to that of ulcerative colitis (86%). However, the simultaneous presence of HHV6 and CMV and/or EBV DNA in ulcerative colitis tissue (76%) was much greater than in either Crohn's disease tissues (38%) or control tissue (29%) (P < 0.05). There was a low prevalence of CMV, HHV6, and EBV DNA in peripheral blood mononuclear cells from all patient groups. CMV and EBV are capable of reactivating HHV6: the high prevalence of coexistent HHV6 infection with either or both of these two viruses in ulcerative colitis tissue suggests that they may play a synergistic role in the pathogenesis of this disease.

Adolescent

Liposome-entrapped antifibrotic agent prevents collagen accumulation in hypertensive pulmonary arteries of rats.

We studied the therapeutic efficacy of an intravenously injected antifibrotic agent encapsulated in liposomes on inhibiting collagen accumulation in hypertensive blood vessels. cis-4-Hydroxy-L-proline (cHyp) in liposomes was injected into rats exposed to 10% O2, and drug effect was evaluated by measuring right ventricular pressure and hydroxyproline content of the pulmonary artery. Right ventricular pressure was 11 +/- 1 mm Hg (mean +/- SEM) 5 days after a single intravenous injection of 200 mg/kg cHyp in liposomes compared with 14 +/- 1 mm Hg in rats injected with empty liposomes; hydroxyproline content was also reduced by cHyp treatment (87 +/- 6 versus 107 +/- 7 micrograms per vessel) (p less than 0.05 for both, n = 6-9). Injections of cHyp in liposomes every 5 days partially prevented hypertension and vascular collagen accumulation during a 3-week exposure to hypoxia, and the dose required was one tenth the dose of unencapsulated cHyp. Therapeutic doses of cHyp in liposomes injected for 6 months affected tensile properties of main pulmonary artery and aorta, but there were no apparent histological effects on other organs. Liposomes injected intravenously were identified in pulmonary artery endothelial cells. The prolonged effect of a single injection of cHyp in liposomes may be due to uptake of the liposomes by the endothelium. Liposome delivery of drugs to the arterial wall may be useful in the study and treatment of hypertensive vascular disease.

Animals

Miniaturization of three carbohydrate analyses using a microsample plate reader.

Three carbohydrate analyses (reducing value by copper-bicinchoninate, total carbohydrate by phenol-sulfuric acid, and D-glucose by glucose oxidase) have been miniaturized using a microsample plate reader. The use of the reducing-value procedure to measure the hydrolysis of starch by alpha-amylase and the use of the glucose oxidase method to measure the hydrolysis of lactose by lactase are illustrated.

Carbohydrates

Human herpesvirus 6 in salivary glands.

In an investigation of the role of saliva in the transmission of human herpesvirus 6 (HHV6) sections of salivary gland tissue were screened for HHV6-specific DNA by in-situ hybridisation and for HHV6-specific protein by immunohistochemical staining with monoclonal antibodies against the virus. All of nine submandibular glands and one of four parotid glands showed the presence of HHV6 genome and expressed protein by these techniques. The findings are consistent with transmission of HHV6 by saliva and suggest that salivary gland tissue is a site of replication of the virus and a potential site for HHV6 persistence.

DNA, Viral

Production of IgM antibody to HHV6 in reactivation and primary infection.

The cross-reaction of HHV6 antibody with that to the other herpesviruses was studied in 96 blood donors whose sera were tested for IgG antibody to human herpesvirus type 6 (HHV6), cytomegalovirus (CMV), Epstein-Barr virus (EBV), varicella zostervirus (VZV) and herpes simplex virus (HSV). No correlation was found between IgG antibody to HHV6 and that to any of the other herpesviruses in these individuals. Antibodies to HHV6 and CMV were measured in patients undergoing documented serological responses to HHV6. Eleven cases of primary HHV6 infection associated with roseola infantum in babies, 1 of whom suffered from gastroenteritis as well as pyrexia and rash, are reported. Three cases of HHV6 reactivation, 1 in a 3-year-old child and 2 in adults, 1 of whom simultaneously underwent a primary CMV infection are also reported. Our results suggest that indirect immunofluorescence is a specific way of measuring HHV6 antibody, that HHV6 IgG and IgM can be detected in the absence of antibody to CMV and that HHV6 IgM is present both in primary HHV6 infections and in reactivations.

Adult

Cytomegalovirus and human herpesvirus-6 in sudden infant death syndrome: an in situ hybridization study.

Thirty lung, spleen, and thymus sections and four lymph node sections from 40 sudden infant death syndrome (SIDS) cases were probed with biotinylated DNA probes specific for human herpesvirus-6 (HHV-6) and cytomegalovirus (CMV). Control material gave a strong, distinct signal with little or no background staining and no cross-reactivity. No staining was found with the SIDS material. We find no evidence to implicate an overwhelming infection by either virus in SIDS.

Cytomegalovirus Infections

Serological prospects for peptide vaccines against foot-and-mouth disease virus.

Antibodies to a synthetic peptide corresponding to the 141 to 160 amino acid sequence of the protein VP1 of type O foot-and-mouth disease virus (FMDV) neutralize a wider range of type O isolates than anti-virion serum. Extending this peptide at the amino terminus reduced the number of strains neutralized by the antipeptide sera. Reactions with antisera to peptides representing non-contiguous native sequences showed that it was also possible to increase the number of strains effectively neutralized. Selected substitutions of a single amino acid at position 148 markedly altered the neutralizing specificity of antibodies elicited by the 141 to 160 peptide. In particular, a peptide with an L----S substitution at this position induced antibodies which neutralized a type O and a type A virus equally, and guinea-pigs inoculated with it were protected from challenge with either virus. Attempts to isolate variant viruses resistant to neutralization with anti-peptide antibody indicated that these occurred at low frequency, and there was some evidence that resistance may be partially conferred by mutations outside the peptide sequence.

Amino Acid Sequence

Comparison of three immunoassays for the detection of anti-HHV6.

Sera from 96 blood donors were tested for antibody to human herpesvirus 6 by indirect immunofluorescence (IF), circle immunoassay (CIA) and competitive radioimmunoassay (RIA). The correlation between the three assays was good but the CIA and competitive RIA were more sensitive for the detection of HHV6 antibody than indirect IF. The crossreaction of HHV6 antibody with that to the other human herpesviruses was also studied in this blood donor group. No correlation was found between antibody to human herpesvirus 6 by any of the methods described and antibody to any of the other human herpesviruses in these sera.

Antibodies, Viral